AstraZeneca Pharmaceuticals (Ireland) Ltd

EMLA 5% w/w Cream

Each gram of cream contains:

Lidocaine 2.5% w/w (25 mg)

Prilocaine 2.5% w/w (25 mg)

Excipients: Contains Polyoxyethylene hydrogenated castor oil (19 mg).

For a full list of excipients, see section 6.1.

Cream

A white, soft, homogeneous aqueous cream.

Topical anaesthesia of the skin in connection with:

- needle insertion, e.g. intravenous catheters or blood sampling;

- superficial surgical procedures

Topical anaesthesia of the genital mucosa, e.g. prior to superficial surgical procedures or prior to infiltration anaesthesia of mucosa.

Topical anaesthesia of leg ulcers to facilitate mechanical cleansing/ debridement.

1) After >5 hours application time anaesthesia decreases.

2) Application for >1 hour has not been documented.

3) Until further clinical data are available, EMLA should not be used in infants up to 12 months of age receiving treatment with methaemoglobin-inducing agents.

4) No clinically significant increase in plasma methaemoglobin levels has been observed after an application time of up to 4 hours on 16 cm².

5) EMLA has been used for the treatment of leg ulcers up to 15 times over a period of 1-2 months without loss of efficacy or increased number or severity of adverse events.

6) Plasma levels have not been determined in patients treated with doses of >10 g, (See also Section 5.2).

7) On female genital skin, EMLA alone applied for 60 or 90 mins does not provide sufficient anaesthesia for thermocautery or diathermy of genital warts.

One gram of EMLA cream pressed out of a tube of 30 g is approximately 3.5 cm.

Persons frequently applying or removing cream should ensure that contact is avoided in order to prevent the development of hypersensitivity.

Hypersensitive to the amide-type anaesthetics or to any other components of the product.

Patients with glucose-6-phosphate dehydrogenase deficiency or congenital or idiopathic methaemoglobinaemia are more susceptible to drug induced signs of methaemoglobinaemia.

EMLA should not be applied to wounds, or to the genital mucosa of children owing to insufficient data on absorption.

In children/ neonates younger than 3 months a transient, clinically insignificant increase in methaemoglobin plasma levels in commonly observed up to 12 hours after an application of EMLA.

Due to insufficient data on absorption of active substances, EMLA should not be applied to open wounds (excluding leg ulcers). Due to the potentially enhanced absorption of newly shaven skin, it is important to adhere to the recommended dosage, area and time of application (see Section 4.2).

Studies have been unable to demonstrate the efficacy of EMLA for heel lancing in neonates.

EMLA should not be applied to the genital mucosa of children owing to insufficient data on absorption of active substances. However, when used in neonates for circumcision, a dose of 1.0 g EMLA on the prepuce has been proven to be safe.

Care should be taken when applying EMLA to patients with atopic dermatitis. A shorter application time, 15-30 minutes, may be sufficient (see Section 5.1). Application times of longer than 30 minutes in patients with atopic dermatitis may result in an increased incidence of local vascular reactions, particularly application site redness and in some cases petechia and purpura (see Section 4.8 Undesirable effects). Prior to removal of mollusca in children with atopic dermatitis it is recommended to apply cream for 30 minutes.

When applied in the vicinity of the eyes, EMLA cream should be used with particular care since it may cause eye irritation. Also the loss of protective reflexes may allow corneal irritation and potential abrasion. If eye contact occurs, immediately rinse the eye with water or sodium chloride solution and protect the eye until sensation returns.

EMLA should not be applied to an impaired tympanic membrane. Tests on laboratory animals have shown that EMLA cream has an ototoxic effect when instilled into the middle ear. Animals with an intact tympanic membrane, however, show no abnormality when exposed to EMLA cream in the external auditory canal.

Patients treated with antiarrhythmics of class III (e.g. amiodarone) should be carefully monitored and ECG monitoring considered as cardiac effects may be additive.

Lidocaine and prilocaine have bacteriocidal and antiviral properties in concentrations above 0.5-2 %. For this reason, although one clinical study suggests that the immunization response, as assessed by local wheal formation, is not affected when EMLA cream is used prior to BCG vaccination, the results of intracutaneous injections of live vaccines should be monitored.

Until further clinical data are available, EMLA should not be used in the following cases:

- in infants up to 12 months of age receiving concomitant treatment with methaemoglobin inducing agents

-in preterm infants with a gestational age less than 37 weeks.

EMLA Cream contains polyoxyethylene hydrogenated castor oil which may cause skin reactions.

Prilocaine in high doses may cause an increase in methaemoglobin plasma levels particularly in conjunction with methaemoglobin-inducing agents (e.g. sulphonamides).

With large doses of EMLA, consideration should be given to the risk of additional systemic toxicity in patients receiving other local anaesthetics or agents structurally related to local anaesthetics, since the toxic effects are additive.

Specific interaction studies with lidocaine/prilocaine and anti-arrhythmic drugs class III (e.g. amiodarone) have not been performed, but caution is advised (see also Section 4.4).

Drugs that reduce the clearance of lidocaine (e.g. cimetidine or betablockers) may cause potentially toxic plasma concentrations when lidocaine is given in repeated high doses over a long time period. Such interactions should therefore be of no clinical importance following short-term treatment with lidocaine (e.g. EMLA cream) at recommended doses.

Animal studies do not indicate any direct or indirect harmful effects on pregnancy, embryo-foetal development, parturition or postnatal development.

Pregnancy

Lactation

EMLA has no influence on driving ability and the ability to operate machines when used at the recommended doses.

1) Intact skin

2) Genital Mucosa

3) Leg ulcer

Rare cases of clinically significant methaemoglobinaemia have been reported. Prilocaine in high doses may cause an increase in the methaemoglobin plasma level particularly in conjunction with methaemoglobin-inducing agents (e.g. sulphonamides).

Clinically significant methaemoglobinaemia should be treated with a slow intravenous injection of methylene blue.

Should other symptoms of systemic toxicity occur, the signs are anticipated to be similar in nature to those following the administration of local anaesthetics by other routes of administration. Local anaesthetic toxicity is manifested by symptoms of nervous system excitation and, in severe cases, central nervous and cardiovascular depression. Severe neurological symptoms (convulsions, CNS depression) must be treated symptomatically by respiratory support and the administration of anticonvulsive drugs, circulatory signs are treated in line with recommendations for resuscitation.

Since the rate of absorption from intact skin is slow, a patient showing signs of toxicity should be kept under observation for several hours following emergency treatment.

Pharmacotherapeutic group: Local anaesthetics of the amide-type,

ATC code: N01B B20

EMLA Cream provides dermal analgesia. The depth of analgesia depends upon the application time and the dose. EMLA causes transient local peripheral vasoconstriction or vasodilation at the treated area.

The use of EMLA prior to subcutaneous measles-mumps-rubella or intramuscular diptheria-pertussis-tetanus-inactivated poliovirus-Haemophilus influenzae b or intramuscular Hepatitis B vaccines does not affect mean antibody titres, rate of seroconversion, or the proportion of patients achieving protective or positive antibody titres post-immunization, as compared to placebo-treated patients.

In patients with atopic dermatitis, a similar but shorter vascular reaction is seen, with erythema occurring after 30-60 minutes, indicating more rapid absorption through the skin (see section 4.5 Special precautions for use).

Systemic absorption of lidocaine and prilocaine from EMLA Cream is dependent upon the dose, area of application and application time. Additional factors include thickness of the skin (which varies in different areas of the body), other conditions such as skin diseases, and shaving.

Intact skin: In order to provide reliable dermal analgesia, EMLA Cream should be applied under an occlusive dressing for 15 minutes on male genital skin, 60 minutes on female genital skin or at least 1 hour on other areas of the skin. The duration of analgesia after an application time of 1-2 hours is at least 2 hours after removal of the dressing.

After application to the thigh in adults (60 g cream/400 cm² for 3 hours) the extent of absorption was approximately 5% of lidocaine and prilocaine. Maximum plasma concentrations (mean 0.12 and 0.07 micrograms/ml) were reached approximately 2-6 hours after the application.

The extent of systemic absorption was approximately 10% following application to the face (10 g/100 cm² for 2 hours). Maximum plasma levels (mean 0.16 and 0.06 micrograms/ml) were reached after approximately 1.5-3 hours.

Genital mucosa: Absorption from the genital mucosa is more rapid than after application to the skin. After the application of 10 g EMLA Cream for 10 minutes to vaginal mucosa maximum plasma concentrations of lidocaine and prilocaine (mean 0.18 micrograms /ml and 0.15 micrograms/ml respectively) were reached after 20-45 minutes.

Lidocaine and prilocaine are well established active ingredients.

A metabolite of lidocaine, 2,6-dimethylaniline, and a metabolite of prilocaine, o-toluidine, showed evidence of mutagenic activity. These metabolites have been shown to have carcinogenicity potential in preclinical toxicological studies evaluating chronic exposure. This has not been shown in subsequent clinical studies.

Risk assessments comparing the calculated maximum human exposure from intermittent use of lidocaine and prilocaine, with the exposure used in preclinical studies, indicate a wide margin of safety for clinical use.

Polyoxyethylene hydrogenated castor oil

Carbomer 974P

Sodium hydroxide for pH adjustment

Purified water

Not applicable.

3 years.

Do not store above 30°C, do not freeze.

Keep the container tightly closed when not in use.

Collapsible aluminium tube with polypropylene cap.

“Pre-medication pack” containing 5 x 5 g tubes EMLA and 12 occlusive dressings.

Pack containing 10 x 5 g tubes of EMLA.

1 x 30 g tube.

1 x 5 g tube.

Not all pack sizes may be marketed.

No special requirements.

AstraZeneca UK Ltd.,

600 Capability Green,

Luton,

LU1 3LU, UK.

PA 970/38/1

25^th April 2008

4^th May 2011